Synthetic heparin disaccharides

1. A disaccharide building block of General Formula XX,

wherein:

X 2 is selected from the group consisting of a hydroxyl group; thioalkyl, thioaryl, halogen, trichloroacetimidoyl, and a t butyldiphenylsilyloxy, and wherein the stereochemistry may be alpha or beta;

R P1 is selected from the group consisting of 4-methoxyphenyl, benzyl, substituted benzyl groups, alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups, and carbonate protecting groups;

R P2 is selected from the group consisting of 4-methoxyphenyl, alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups, carbonate protecting groups, carbamate protecting groups, and C 3 -C 5 alkenyl;

R E1 is selected from the group consisting of methyl, C 2 -C 5 alkyl, substituted C 2 -C 5 alkyl, C 3 -C 5 alkenyl, benzyl and substituted benzyl groups;

R B1 is selected from the group consisting of an azido function, an amine, an NH-Dde and an NH-DTPM group, or R H2 and R B1 can combine together to form a cyclic carbamate;

R H is benzyl;

R H2 is selected from the group consisting of benzyl, substituted benzyl protecting group, allyl, and allyloxycarbonyl, or R H2 and R B1 independently can combine together to form a cyclic carbamate; and

R S5 is selected from the group consisting of benzoyl, arylacyl or alkylarylacyl, and substituted alkylacyl, 4-chlorobenzoyl, arylacyl or alkylarylacyl protecting groups, allyloxycarbonyl, ethoxycarbonyl, tertbutoxycarbonyl, carbonate protecting groups, a t butyldiphenylsilyl, allyl, methoxymethyl, methoxyethyl, and benzyloxymethyl.

2. The disaccharide building block of claim 1 ,

wherein:

R P2 is selected from the group consisting of alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups;

R E1 is selected from the group consisting of methyl, C 2 -C 5 alkyl, substituted C 2 -C 5 alkyl, benzyl, and substituted benzyl groups;

R H2 is selected from the group consisting of benzyl and substituted benzyl protecting group; or R H2 and R B1 independently can combine together to form a cyclic carbamate;

R H is benzyl; and

R S5 is C 6 to C 13 arylacyl or alkylarylacyl, and substituted C 3 to C 6 alkylacyl, C 6 to C 13 arylacyl or alkylarylacyl protecting groups, carbonate protecting groups, and tert-Butyldiphenylsilyl.

3. The disaccharide building block of claim 1 ,

wherein:

X 2 is selected from the group consisting of tertbutyldiphenylsilyloxy, trichloroacetimidoyl, and fluoro; and wherein the stereochemistry may be alpha or beta;

R E1 is selected from the group consisting of methyl, allyl, and benzyl;

R P1 is benzyl;

R P2 is selected from the group consisting of benzoyl and allyloxycarbonyl;

R H is benzyl;

R H2 is benzyl; and

R S5 is selected from the group consisting of 4-methoxyphenyl, 4-methoxybenzyl, benzoyl, and tert-butyldiphenylsilyl.

4. A disaccharide building block of General Formula XXI,

wherein:

X 2 is selected from the group consisting of a hydroxyl group, thioalkyl, thioaryl, halogen, trichloroacetimidoyl, t butyldiphenylsilyloxy; and wherein the stereochemistry may be alpha or beta;

R P1 is selected from the group consisting of 4-methoxyphenyl, benzyl, substituted benzyl groups, alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups, and carbonate protecting groups;

R P2 is selected from the group consisting of 4-methoxyphenyl, benzyl, substituted benzyl groups, alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups, carbonate protecting groups, silyl protecting groups, carbamate protecting groups, and C 3 -C 5 alkenyl;

R B1 is selected from the group consisting of an azido function, an amine, an NH-Dde and an NH-DTPM group; or R H2 and R B1 can combine together to form a cyclic carbamate;

R H is selected from the group consisting of benzyl, substituted benzyl protecting group, allyl, and allyloxycarbonyl;

R H2 is selected from the group consisting of benzyl, substituted benzyl protecting group, allyl, and allyloxycarbonyl; or R H2 and R B1 independently can combine together to form a cyclic carbamate;

R S5 is selected from the group consisting of 4-methoxyphenyl; substituted benzyl groups; alkylacyl, arylacyl or alkylarylacyl, and substituted alkylacyl, arylacyl or alkylarylacyl protecting groups, carbonate protecting groups, t butyldiphenylsilyl, allyl, methoxymethyl, methoxyethyl, and benzyloxymethyl;

or R S5 and R H can be combined to form a cyclic acetal or ketal moiety; and

R M is selected from the group consisting of a p-methoxyphenyl protecting group and a trityl group.

5. The disaccharide building block of claim 4 ,

wherein:

R P2 is selected from the group consisting of 4-methoxyphenyl, benzyl, substituted benzyl groups, alkylacyl, arylacyl and alkylarylacyl, or substituted alkylacyl, arylacyl and alkylarylacyl protecting groups, and carbonate protecting groups;

R H2 is selected from the group consisting of benzyl and substituted benzyl protecting group; or R H2 and R B1 independently can combine together to form a cyclic carbamate;

R H is selected from the group consisting of benzyl and substituted benzyl protecting group; and

R S5 is selected from the group consisting of 4-methoxyphenyl, substituted benzyl groups, alkylacyl, arylacyl or alkylarylacyl, and substituted alkylacyl, arylacyl or alkylarylacyl protecting groups, carbonate protecting groups, and tert-Butyldiphenylsilyl.

6. The disaccharide building block of claim 4 ,

wherein:

X 2 is selected from the group consisting of a thiomethyl, thiocresyl, trichloroacetimidoyl and tert-butyldiphenylsilyl, and wherein the stereochemistry may be alpha or beta;

R P1 is benzyl;

R P2 is selected from the group consisting of benzyl, benzoate, and allyloxycarbonyl;

R B1 is an azido function, or R H2 and R B1 can combine together to form a cyclic carbamate;

R H2 is benzyl;

R H is benzyl;

R S5 is selected from the group consisting of 4-methoxyphenyl, 4-methoxybenzyl, benzoyl, and tert-butyldiphenylsilyl; and

R M is selected from the group consisting of a p-methoxyphenyl, 4-methoxybenzyl and a trityl group.

7. A disaccharide building block of General Formula XX,

wherein:

X 2 is selected from the group consisting of thioalkyl, thioaryl, fluoro, trichloroacetimidoyl, and t butyldiphenylsilyloxy; and wherein the stereochemistry may be alpha or beta;

R P1 is selected from the group consisting of 4-methoxyphenyl, benzyl, a substituted benzyl group, an alkylacyl, arylacyl, or alkylarylacyl or a substituted alkylacyl, arylacyl or alkylarylacyl protecting group, and a carbonate protecting group;

R P2 is selected from the group consisting of an alkylacyl, arylacyl or alkylarylacyl or a substituted alkylacyl, arylacyl or alkylarylacyl protecting group, a carbonate protecting group, a carbamate protecting groups, and C 3 -C 5 alkenyl;

R E1 is selected from the group consisting of methyl, C 2 -C 5 alkyl, substituted C 2 -C 5 alkyl, C 3 -C 5 alkenyl, benzyl, and a substituted benzyl group;

R B1 is selected from the group consisting of an azido function, an amine, an NH-Dde and an NH-DTPM group; or R H2 and R B1 can combine together to form a cyclic carbamate;

R H is selected from the group consisting of benzyl, a substituted benzyl protecting group, allyl, and allyloxycarbonyl;

R H2 is selected from the group consisting of benzyl, a substituted benzyl protecting group, allyl, and allyloxycarbonyl; or R H2 and R B1 independently can combine together to form a cyclic carbamate; and

R S5 is selected from the group consisting of 4-methoxyphenyl, a substituted benzyl group, benzoyl, an alkylacyl or alkylarylacyl or a substituted alkylacyl, arylacyl, or alkylarylacyl protecting group, allyloxycarbonyl, ethoxycarbonyl, tertbutoxycarbonyl, a carbonate protecting group, t butyldiphenylsilyl, allyl, methoxymethyl, methoxyethyl, and benzyloxymethyl; or R S5 and R H can be combined to form a cyclic acetal or ketal moiety.

8. The disaccharide building block of claim 7 ,

wherein:

R P2 is selected from the group consisting of an alkylacyl, arylacyl, alkylarylacyl, substituted alkylacyl, arylacyl, alkylarylacyl protecting groups, and a carbonate protecting group;

R E1 is selected from the group consisting of methyl, C 2 -C 5 alkyl, substituted C 2 -C 5 alkyl, benzyl, and a substituted benzyl group;

R H2 is selected from the group consisting of benzyl and a substituted benzyl protecting group; or R H2 and R B1 independently can combine together to form a cyclic carbamate;

R H is benzyl; and

R S5 is selected from the group consisting of C 3 -C 6 alkylacyl, C 6 -C 13 arylacyl or alkylarylacyl, a substituted C 3 to C 6 alkylacyl, C 6 to C 13 arylacyl, alkylarylacyl protecting group, a carbonate protecting group, and tert-Butyldiphenylsilyl.

9. The disaccharide building block of claim 7 ,

wherein:

X 2 is selected from the group consisting of tertbutyldiphenylsilyloxy, trichloroacetimidoyl, and fluoro; and wherein the stereochemistry may be alpha or beta;

R E1 is selected from the group consisting of methyl, allyl, and benzyl;

R P1 is benzyl;

R P2 is selected from the group consisting of benzoyl and allyloxycarbonyl;

R H is benzyl;

R H2 is benzyl; and

R S5 is selected from the group consisting of 4-methoxyphenyl, 4-methoxybenzyl, benzoyl, and tert-Butyldiphenylsilyl.

10. A disaccharide represented by the formula:

11. A disaccharide represented by the formula:

12. A disaccharide represented by the formula:

13. A disaccharide of the Formula:

wherein:

X 2 is selected from the group consisting of thioalkyl, thioaryl, fluoro, trichloroacetimidoyl, a t butyldiphenylsilyloxy; and wherein the stereochemistry may be alpha or beta;

R E1 is selected from the group consisting of methyl, C 2 -C 5 alkyl, and benzyl;

R P2 is selected from the group consisting of arylacyl, alkylarylacyl, and substituted alkylacyl; and,

R S5 is selected from the group consisting of alkylacyl, arylacyl, substituted alkylacyl, arylacyl, or alkylarylacyl, tert-Butyldiphenylsilyl.